The number of B-adrenergic receptor (BAR) fluctuates with changes in the neuronal activity in vivo. Two extremities of this receptor plasticity are the supersensitivity and subsensitivity; the latter often involves the loss of receptor site, termed down-regulation. We have used a model system of frog erythrocyte to study the molecular mechanisms of Beta-receptor down-regulation induced by isoproterenol stimulation. Our previous studies have provided the first evidence that agonist-induced down regulation of BAR is associated with internalization of BAR sites in frog erythrocytes. This receptor internalization is causative for the desensitization of adenylate cyclase to BAR stimulation. Internalized BAR sites are sequestered in endocytotic vesicles with molecular weight more than 20 x 10-6 daltons and are recycled to the plasma membrane during receptor resensitization. Moreover, mechanisms of coated pit and coated vesicle may be involved in this receptor internalization and down-regulation. In the present study we have succeeded in staining BAR in frog erythrocytes using BAR specific antibody and detected important differences in the receptor staining pattern during receptor desensitization and down-regulation. Currently we are attempting to elucidate the details of molecular events at the electron microscopic level using this morphological approach. Moreover, we have investigated whether BAR internalization occurs in the CNS. Purified coated vesicles isolated from bovine brain were found to contain BAR which was uncoupled to the GTP binding protein and adenylate cyclase. These BAR sites were labeled by a liphophilic ligand 125I-cyanopindolol but not by a hydrophilic ligand 3H-CGP-12177. This data suggest that BAR may be internalized by coated vesicle-mechanisms in the CNS. Thus, BAR internalization might play an important role in the CNS plasticity.